Arthur C. Corcoran Memorial Lecture. The role of eicosanoids in angiotensin-dependent hypertension.
Many eicosanoids produced in vascular and renal structures are endowed with the ability to influence vascular and renal mechanisms of blood pressure regulation. Eicosanoids subserve both prohypertensive and antihypertensive mechanisms. The development of angiotensin-dependent hypertension in rats is accompanied by increased vascular production of thromboxane A2 (TXA2) and of lipoxygenase-derived products with the ability to inhibit prostacyclin synthase. As a result of these abnormalities, the activity of pressor mechanisms mediated by TXA2 and/or prostaglandin (PG) H2 is increased. The cancellation of TXA2- and/or of PGH2-mediated pressor mechanisms, after treatment with thromboxane synthase inhibitors or TXA2/PGH2 receptor blockers, lowers blood pressure in rats with angiotensin-dependent hypertension. Inhibitors of lipoxygenase also lower blood pressure in such animals, in part by decreasing the synthesis of lipoxygenase-derived inhibitors of prostacyclin synthase. Thus, the vasodepressor effect of these agents is accompanied by increased vascular formation of PGI2 and can be prevented by cyclooxygenase inhibitors. Cyclooxygenase-derived eicosanoids, PGE2 and PGI2, also subserve antihypertensive mechanisms in angiotensin-dependent models of hypertension. The level of blood pressure in such models of hypertension reflects, in part, the interplay among prohypertensive and antihypertensive functions subserved by cyclooxygenase- and lipoxygenase-derived eicosanoids.
Nasjletti
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Department of Pharmacology, New York Medical College, Valhalla, USA.
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure; D001808:Blood Vessels / Q000502:physiology / Q000503:physiopathology; D015777:Eicosanoids / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000502:physiology / Q000503:physiopathology; D008084:Lipoxygenase / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats
D015777:Eicosanoids; D000804:Angiotensin II; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases